Safety and Efficacy of Vadadustat Versus Darbepoetin Alfa for Chronic Kidney Disease-Related Anemia in Patients Receiving Dialysis by Baseline Erythropoiesis-Stimulating Agent Dose.

introductionErythropoiesis-stimulating agents (ESAs) and iron supplementation are standard treatments for chronic kidney disease (CKD)-related anemia. Targeting higher hemoglobin values in CKD increases cardiovascular risk. Whether the increased risk is from higher ESA doses or higher hemoglobin levels is uncertain, but alternative therapies are sought for patients requiring high ESA doses. Phase 3 INNO

methodsWe compared the safety and efficacy of vadadustat versus darbepoetin alfa across prespecified baseline ESA dose subgroups (low [≤ 90 U/kg/week], intermediate [> 90 and < 300 U/kg/week], or high [≥ 300 U/kg/week]) in the INNO

findingsCompared with darbepoetin alfa, first MACE hazard ratios for vadadustat were 0.99 (95% CI, 0.81-1.23), 0.93 (95% CI, 0.74-1.18), and 0.62 (95% CI, 0.34-1.14) for low, intermediate, and high baseline ESA dose subgroups, respectively (interaction p = 0.92). Vadadustat was noninferior to darbepoetin alfa in hemoglobin change from baseline to primary evaluation period, with mean differences (vadadustat-darbepoetin alfa) of -0.10 g/dL (95% CI, -0.19 to -0.02), -0.20 g/dL (95% CI, -0.30 to -0.09), and -0.39 g/dL (95% CI, -0.67 to -0.11) for low, intermediate, and high ESA dose subgroups, respectively. DISCUSSION: Comparing safety and efficacy by baseline ESA dose among patients with CKD on maintenance dialysis, vadadustat was noninferior to darbepoetin alfa for all ESA dose subgroups, including patients with high baseline ESA requirements.